A cross-sectional design was used to examine the mediating effect of physical activity between dyspnea and fatigue in patients with chronic obstructive pulmonary disease (COPD). Dyspnea was measured using a vertical visual analogue scale, fatigue using the Profile of Mood States-Fatigue subscale, and physical activity using the 6-minute-walk (6MW) test. A convenience sample of 17 male and 22 female patients with COPD provided data for analysis. The sample was characterized by relatively high forced expiratory volume in 1 second (FEV1) of predicted normal values, indicating mild lung impairment and high mean levels of fatigue and dyspnea. Controlling for age and FEV1, dyspnea, physical activity, and fatigue were significantly interrelated. Results of the regression analysis suggested the mediating function of physical activity between dyspnea and fatigue. Limitations and suggestions for practice and future research are presented.